Epstein-barr virus vaccines
Inventors
Kanekiyo, Masaru • Nabel, Gary J. • Cohen, Jeffrey • Bu, Wei
Assignees
US Department of Health and Human Services
Publication Number
US-12005115-B2
Publication Date
2024-06-11
Expiration Date
2034-10-10
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Abstract
Vaccines are provided that elicit neutralizing antibodies to Epstein-Barr virus (EBV). Some vaccines comprise nanoparticles that display envelope proteins from EBV on their surface. The nanoparticles comprise fusion proteins comprising a monomeric subunit of a self-assembly protein, such as ferritin, joined to at least a portion of an EBV envelope protein. The fusion proteins self-assemble to form the envelope protein-displaying nanoparticles. Such vaccines can be used to vaccinate an individual against infection by different types of Epstein-Barr viruses as well as Epstein-Barr viruses that are antigenically divergent from the virus from which the EBV envelope protein was obtained. Also provided are fusion proteins and nucleic acid molecules encoding such proteins.
Core Innovation
The invention provides novel, nanoparticle-based vaccines for Epstein-Barr virus (EBV) that are easily manufactured, potent, and elicit neutralizing antibodies to EBV. Specifically, vaccines comprise nanoparticles displaying envelope proteins from EBV on their surface. These nanoparticles consist of fusion proteins, each comprising a monomeric subunit of a self-assembly protein, such as ferritin, joined to an immunogenic portion of an EBV envelope protein. The fusion proteins self-assemble to form envelope protein-displaying nanoparticles, which can vaccinate individuals against different types of EBV and antigenically divergent EBV strains.
The problem addressed is the absence of an efficacious EBV vaccine despite continued vaccine efforts. EBV infects the majority of adults worldwide and is associated with infectious mononucleosis and human cancers, creating a substantial public health burden. Previous vaccines, such as a recombinant gp350 protein vaccine, did not prevent infection and only reduced incidence of infectious mononucleosis. Thus, there is a need for a vaccine providing robust protection against EBV infection.
The invention solves this by providing fusion proteins combining EBV envelope proteins with self-assembly proteins, yielding nanoparticles that present EBV proteins in a multimeric form on their surface. These ENV-SA fusion proteins induce potent neutralizing antibody responses, including broadly neutralizing antibodies effective against heterologous and antigenically divergent EBV strains. The nanoparticle vaccines elicit stronger and more durable immune responses than soluble EBV envelope proteins. The invention also encompasses nucleic acid molecules encoding the fusion proteins, recombinant cells and viruses expressing the fusion proteins, methods for production, and methods of vaccination using the nanoparticles.
Claims Coverage
The claims include one independent claim covering a nucleic acid molecule encoding a recombinant protein fusion of a self-assembling protein subunit and an EBV envelope protein. The main inventive features relate to the composition of the fusion protein and its sequence identity.
Encoding of fusion protein comprising a self-assembling monomeric subunit and EBV gp350 envelope protein
A nucleic acid molecule encoding a recombinant protein that comprises at least 25 contiguous amino acids from a monomeric subunit protein capable of self-assembling into a nanoparticle, joined to at least one immunogenic portion from the Epstein-Barr virus (EBV) envelope protein gp350.
Sequence identity to specified variants among fusion proteins
The recombinant protein encoded comprises an amino acid sequence with at least 80% identity to sequences selected from SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:77 and SEQ ID NO:80, representing variants of the fusion protein.
The claims cover nucleic acid molecules encoding fusion proteins combining a monomeric self-assembling protein subunit and the EBV gp350 envelope protein, specifically sequences with at least 80% identity to defined variants. This underpins vaccines composed of nanoparticles formed from these fusion proteins.
Stated Advantages
The vaccine is easily manufactured.
The vaccine is potent and elicits neutralizing antibodies to Epstein-Barr virus.
The vaccine can protect against infection by different EBV types and antigenically divergent strains.
Nanoparticles presenting EBV proteins induce a more robust immune response compared to soluble proteins.
Vaccines reduce incidence of Epstein-Barr virus-associated diseases including infectious mononucleosis and malignancies.
Documented Applications
Vaccination of individuals to elicit neutralizing immune responses against Epstein-Barr virus infection.
Producing vaccines comprising nanoparticles displaying EBV envelope proteins to prevent EBV infection.
Using fusion proteins comprising self-assembling protein subunits joined to EBV envelope proteins for vaccine manufacture.
Administration in prime/boost immunization protocols with monovalent or multivalent nanoparticle vaccine compositions.
Protecting against infection by heterologous or antigenically divergent Epstein-Barr virus strains.
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